The regulator of capsule synthesis (Rcs) system is a non-orthodox two-component regulatory system found in many members of Enterobacteriaceae. This system consists of three core proteins (the transmembrane sensor kinase RcsC, the transmembrane protein RcsD and the response regulator RcsB) and multiple accessory proteins. Rcs system can integrate environmental signals, regulate gene expression and alter the physiological behavior of bacteria. Defining the environmental response mechanism of Rcs system in Enterobacteria has been a major focus in several recent studies. Here, the role of Rcs system in signal perception and conduction, and the target genes regulated by Rcs system and their life phenomena are introduced. This review will highlight the current understanding of the biological role of Rcs system, as well as to provide a theoretical basis for the development of new strategies for bacterial control, prevention and treatment.